Medical education and health promotion of communities: the articulation of these practices on an equal footing

Submitted by Gilvan Almeida ([email protected]) on 2016-08-10T18:28:53Z No. of bitstreams: 2 1082.pdf: 831912 bytes, checksum: e797a529904a29f4c5595167931117f0 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Maria Arruda ([email protected]) on 2017-12-06T12:12:35Z (GMT) No. of bitstreams: 2 1082.pdf: 831912 bytes, checksum: e797a529904a29f4c5595167931117f0 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2017-12-06T12:12:35Z (GMT). No. of bitstreams: 2 1082.pdf: 831912 bytes, checksum: e797a529904a29f4c5595167931117f0 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.O presente estudo procurou discutir sobre as necessárias modificações na formação médica impulsionadas a partir da instituição das Diretrizes Curriculares Nacionais do Curso de Graduação em Medicina, articulando-a com a nova Promoção da Saúde. Fez-se uma revisão da história da medicina e do processo de trabalho em saúde, contextualizando-os. Ressaltou-se a importância da integralidade do cuidado como referencial tanto para se alcançar a almejada Promoção da Saúde quanto para a formação de profissionais capazes de lidar com a saúde e seus determinantes. O trabalho tem como objeto de estudo as atividades práticas realizadas por estudantes do primeiro ano de graduação de medicina de uma Instituição de Ensino Superior. Trata-se de um estudo qualitativo descritivo que utilizou como técnicas a produção de dados primários e a busca de dados secundários

Ad limina. Frontiere e contaminazioni transdisciplinari nella storia delle scienze

Il volume raccoglie gran parte dei contributi presentati in occasione del Convegno Nazionale della Società Italiana di Storia della Scienza (SISS), tenutosi a Catania, dal 30 maggio al 1° giugno 2022, nella prestigiosa sede del Dipartimento di Scienze Umanistiche dell’Università etnea. Ad limina. Frontiere e contaminazioni transdisciplinari nella storia delle scienze, oltre a essere il titolo che la Società ha scelto per questo evento, è diventato un momento di grande dibattito e confronto sulla complessità e sull’attualità della storia delle scienze e delle tecniche, oltre che sull’importante ruolo che questa disciplina ha assunto negli ultimi anni. Proprio nel 2022, la SISS giunge al quarantesimo anno dalla sua fondazione: il ritorno a un convegno in presenza e la pubblicazione di questi atti sono certamente il modo migliore per festeggiare questo importante traguardo

The Discovery of RNA Aptamers that Selectively Bind Glioblastoma Stem Cells

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite progress in surgical and medical neuro-oncology, prognosis for GBM patients remains dismal, with a median survival of only 14-15 months. The modest benefit of conventional therapies is due to the presence of GBM stem cells (GSCs) that cause tumor relapse and chemoresistance and, therefore, that play a key role in GBM aggressiveness and recurrence. So far, strategies to identify and target GSCs have been unsuccessful. Thus, the development of an approach for GSC detection and targeting would be fundamental for improving the survival of GBM patients. Here, using the cell-systematic evolution of ligand by exponential (SELEX) methodology on human primary GSCs, we generated and characterized RNA aptamers that selectively bind GSCs versus undifferentiated GBM cells. We found that the shortened version of the aptamer 40L, which we have called A40s, costained with CD133-labeled cells in human GBM tissue, suggestive of an ability to specifically recognize GSCs in fixed human tissues. Of note, both 40L and A40s were rapidly internalized by cells, allowing for the delivery of the microRNA miR-34c and the anti-microRNA anti-miR-10b, demonstrating that these aptamers can serve as selective vehicles for therapeutics. In conclusion, the aptamers 40L and A40s can selectively target GSCs. Given the crucial role of GSCs in GBM recurrence and therapy resistance, these aptamers represent innovative drug delivery candidates with a great potential in the treatment of GBM

RagD auto-activating mutations impair MiT/TFE activity in kidney tubulopathy and cardiomyopathy syndrome

: Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are "auto- activating", even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation of "canonical" mTORC1 substrates, such as S6K. By using HeLa and HK-2 cell lines, human induced pluripotent stem cell-derived cardiomyocytes and patient-derived primary fibroblasts, we show that RRAGD auto-activating mutations lead to inhibition of TFEB and TFE3 nuclear translocation and transcriptional activity, which impairs the response to lysosomal and mitochondrial injury. These data suggest that inhibition of MiT/TFE factors plays a key role in kidney tubulopathy and cardiomyopathy syndrome

TFEB and TFE3 drive kidney cystogenesis and tumorigenesis

: Birt-Hogg-Dubé (BHD) syndrome is an inherited familial cancer syndrome characterized by the development of cutaneous lesions, pulmonary cysts, renal tumors and cysts and caused by loss-of-function pathogenic variants in the gene encoding the tumor-suppressor protein folliculin (FLCN). FLCN acts as a negative regulator of TFEB and TFE3 transcription factors, master controllers of lysosomal biogenesis and autophagy, by enabling their phosphorylation by the mechanistic Target Of Rapamycin Complex 1 (mTORC1). We have previously shown that deletion of Tfeb rescued the renal cystic phenotype of kidney-specific Flcn KO mice. Using Flcn/Tfeb/Tfe3 double and triple KO mice, we now show that both Tfeb and Tfe3 contribute, in a differential and cooperative manner, to kidney cystogenesis. Remarkably, the analysis of BHD patient-derived tumor samples revealed increased activation of TFEB/TFE3-mediated transcriptional program and silencing either of the two genes rescued tumorigenesis in human BHD renal tumor cell line-derived xenografts (CDXs). Our findings demonstrate in disease-relevant models that both TFEB and TFE3 are key drivers of renal tumorigenesis and suggest novel therapeutic strategies based on the inhibition of these transcription factors